10-96602274-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152309.3(PIK3AP1):c.2360+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PIK3AP1
NM_152309.3 splice_donor_region, intron
NM_152309.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001063
2
Clinical Significance
Conservation
PhyloP100: -0.0540
Genes affected
PIK3AP1 (HGNC:30034): (phosphoinositide-3-kinase adaptor protein 1) Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in regulation of inflammatory response; regulation of signal transduction; and toll-like receptor signaling pathway. Predicted to be located in cytoplasm and membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.2360+6A>G | splice_donor_region_variant, intron_variant | ENST00000339364.10 | NP_689522.2 | |||
LOC105378443 | XR_946220.4 | n.1447-5402T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.2360+6A>G | splice_donor_region_variant, intron_variant | 1 | NM_152309.3 | ENSP00000339826 | P1 | |||
PIK3AP1 | ENST00000371109.3 | c.1157+6A>G | splice_donor_region_variant, intron_variant | 1 | ENSP00000360150 | |||||
PIK3AP1 | ENST00000371110.6 | c.1826+6A>G | splice_donor_region_variant, intron_variant | 2 | ENSP00000360151 | |||||
PIK3AP1 | ENST00000467625.5 | n.557+6A>G | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.95e-7 AC: 1AN: 1439102Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 716834
GnomAD4 exome
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1
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1439102
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29
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0
AN XY:
716834
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 15, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with PIK3AP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 16 of the PIK3AP1 gene. It does not directly change the encoded amino acid sequence of the PIK3AP1 protein, but it affects a nucleotide within the consensus splice site of the intron. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at